The broad, long-term objective of the proposed research is to lessen the effects of pulmonary barotrauma in ventilated patients. These include, in addition to pneumothorax, progressive impairment of pulmonary mechanics, alveolar cell dysfunction, and changes in lung fluid balance and blood-gas barrier permeability. The overall hypothesis is that mechanical ventilation which results in large lung volumes (in contrast to pressure) produced either dynamically or statically, can result in large deformations of the alveolar epithelial lining with subsequent alveolar cell injury. In specific aim one lung volume of rats will be related to alveolar epithelial surface area by morphometric techniques. From these measurements the range of strains applied to the alveolar epithelial surface will be calculated. In Aim 2, cultured alveolar epithelial cells (both type II cells and cells maintained in culture exhibiting characteristics of type I cells) will be subjected to patterns of biaxial deformation spanning and exceeding physiologic ranges. Changes in cell viability will be measured by LDH assays, cell metabolic activity by ATP assays and, for the so-called type I cells, changes in monolayer permeability by changes in transepithelial resistance and short circuit current. In specific aim three rats will be ventilated with frequencies and at volumes which should subject the lung and particularly the epithelium to small, medium, and large deformations. Alterations in wet-dry ratio will be considered an index of extravascular water. Alveolar fluid volume measured by the dilution of dextran in BAL fluid and alveolar concentration of fluorescein labeled albumin in blood will be used as indices of alveolar edema and permeability to large molecules respectively.